Female mice from experimental populations (females + one male) develop ovarian lesions of the corpora lutea (CLs). The lesions appear to contain amyloid protein and organelle debris originating presumably from cells within CLs exhibiting atypical or incomplete luteolysis. At least three factors appear to be involved in the etiology: social stress resulting from high population density, female aggressive behavior, and advancing age. The alteration in behavior and the dysfunctional ovaries suggest changes in endocrine function and possibly in immune system mechanisms. As populations near maximum density, reproduction ceases and females exhibit male-like behavior, which we speculate may result from increased ovarian androgen production. The purpose of the proposed research is to study the relationship between population stress and the induction of ovarian lesions. The specific aims will be carried out by comparing females from the following population types: small baseline, medium sized, large sized, and "assembled." Additional manipulations will include establishing these populations as either freely growing or as the all female + one male populations. Our plan is to: 1) monitor population dynamics including density and social behavior; 2) characterize reproductive function; 3) determine the nature of the ovarian lesions more fully; 4) characterize circulating hormone levels (pituitary, gonadal and adrenal); 5) analyze immunologically important proteins; 6) characterize the cellular immune system; 7) study ovarian cellular enzyme-marker distributions; and 8) monitor ovarian oxygen consumption and energy utilization. Successful conclusion of this project will provide a comprehensive analysis of the physiological and behavioral correlates of population stress on the induction of ovarian lesions of the corpora lutea. This is one example of the effects of an altered social environment on an individual's ability to maintain its homeostasis. The information learned during the course of this study may be useful as a basis for interpreting the role of social stress on reproductive function in women.